Ezetimibe and atorvastatin Sandoz

Patient Information Leaflet

Ezetimibe and Atorvastatin Sandoz 10 mg/10 mg film-coated tablets, mg/20 mg film-coated tablets, mg/40 mg film-coated tablets, mg/80 mg film-coated tablets

Generic medicine
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful to them.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Ezetimibe and Atorvastatin Sandoz is and what it is used for
2. What you need to know before taking Ezetimibe and Atorvastatin Sandoz
3. How to take Ezetimibe and Atorvastatin Sandoz
4. Possible side effects
5. How to store Ezetimibe and Atorvastatin Sandoz
6. Contents of the pack and other information

1. What Ezetimibe and Atorvastatatin Sandoz is and what it is used for

Ezetimibe and Atorvastatin Sandoz is a medicine used to lower cholesterol levels. Ezetimibe and Atorvastatin Sandoz contains ezetimibe and atorvastatin.
Ezetimibe and Atorvastatin Sandoz is used in adults to lower blood levels of total cholesterol, "bad" cholesterol (LDL cholesterol), and fatty substances called triglycerides. In addition, Ezetimibe and Atorvastatin Sandoz increases levels of "good" cholesterol (HDL cholesterol).
Ezetimibe and Atorvastatin Sandoz works in two ways to lower cholesterol. It reduces cholesterol absorbed from the digestive tract, as well as cholesterol naturally produced by the body.
Cholesterol is one of several fatty substances found in the bloodstream. Total cholesterol consists mainly of LDL cholesterol and HDL cholesterol.
LDL cholesterol is often called "bad" cholesterol because it can accumulate in the walls of arteries, forming plaques. Over time, this plaque buildup can lead to narrowing of the arteries. This narrowing can slow down or block blood flow to vital organs such as the heart and brain. Such blockage of blood flow can cause a heart attack or stroke.
HDL cholesterol is often called "good" cholesterol because it helps prevent bad cholesterol from building up in the arteries and protects against heart disease.
Triglycerides are another form of fat present in the blood that may increase the risk of heart disease.
Ezetimibe and Atorvastatin Sandoz is used for patients who cannot control their cholesterol levels with diet alone. While taking this medicine, you must still follow a cholesterol-lowering diet.
Ezetimibe and Atorvastatin Sandoz is used as an add-on therapy to diet to lower cholesterol if you have:

• elevated cholesterol levels in the blood (primary hypercholesterolaemia) [heterozygous familial and non-familial] or elevated levels of fats in the blood (mixed hyperlipidaemia):
  • that are not well controlled by a statin alone;
  • for which you have previously been treated with a statin and ezetimibe as separate tablets;
• an inherited disease (homozygous familial hypercholesterolaemia) that increases your blood cholesterol levels. You may also be receiving other treatments.
• heart disease. Ezetimibe and Atorvastatin Sandoz reduces the risk of heart attack, stroke, surgical procedures to improve blood flow to the heart, or hospitalisation due to chest pain.

Ezetimibe and Atorvastatin Sandoz does not help with weight loss.

2. What you need to know before taking Ezetimibe and Atorvastatin Sandoz

Do not take Ezetimibe and Atorvastatin Sandoz if

• you are allergic to ezetimibe, atorvastatin, or any of the other ingredients of this medicine (listed in section 6)
• you have or have ever had liver disease
• you have had unexplained abnormal results in blood tests assessing liver function
• you are a woman of childbearing age and you are not using a reliable method of contraception
• you are pregnant, trying to become pregnant, or breastfeeding
• you are taking the combination of glecaprevir/pibrentasvir medicines for the treatment of hepatitis C

Warnings and precautions
Talk to your doctor or pharmacist before taking Ezetimibe and Atorvastatin Sandoz if:

• you have previously had a stroke with cerebral haemorrhage or if there are small accumulations of fluid in the brain due to previous strokes
• you have kidney problems
• you have an underactive thyroid gland (hypothyroidism)
• you have had repeated or unexplained episodes of muscle discomfort or pain, or have a personal or family history of muscle disorders
• you have previously had muscle problems during treatment with other lipid-lowering medicines (e.g., other "statin" or "fibrate" medicines)
• you regularly consume large amounts of alcohol
• you have a history of liver disease
• you are over 70 years old
• you are taking or have taken within the last 7 days an oral or injectable medicine called fusidic acid (used to treat bacterial infection). The combination of fusidic acid and Ezetimibe and Atorvastatin Sandoz may lead to serious muscle problems (rhabdomyolysis). (See section “Other medicines and Ezetimibe and Atorvastatin Sandoz”.)
• your doctor has diagnosed you with intolerance to certain sugars; contact them before taking this medicine
• you have or have had myasthenia (a disease characterised by generalised muscle weakness, including in some cases the muscles used for breathing) or ocular myasthenia (a disease causing weakness of the eye muscles), as statins may sometimes worsen myasthenia or cause its onset (see section 4).
• you are taking or have taken within the last 7 days fusidic acid (used to treat bacterial infection) by mouth or injection. The combination of fusidic acid and Ezetimibe and Atorvastatin Sandoz can cause serious muscle problems (rhabdomyolysis).

Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness
while taking Ezetimibe and Atorvastatin Sandoz.
This is because, although rarely, muscle problems can be severe, including muscle breakdown leading to kidney damage. It is known that atorvastatin can cause muscle problems, and cases of muscle problems have also been reported with ezetimibe.
Additionally, inform your doctor or pharmacist if you have persistent muscle weakness. Further tests and treatment may be needed.
Consult your doctor or pharmacist before taking Ezetimibe and Atorvastatin Sandoz:

• if you have severe respiratory insufficiency

If any of these conditions apply to you (or you are unsure), inform your doctor or pharmacist before taking Ezetimibe and Atorvastatin Sandoz, as your doctor may need to perform a blood test before and possibly during treatment to assess the risk of muscle-related side effects. It is known that the risk of muscle-related adverse effects (e.g., rhabdomyolysis) increases when certain medicines are taken concomitantly (see section 2 “Other medicines and Ezetimibe and Atorvastatin Sandoz”).
During treatment with this medicine, your doctor will monitor you closely if you have diabetes or are at risk of developing diabetes. Risk factors for developing diabetes include high levels of sugar and fats in the blood, being overweight, and having high blood pressure.
Inform your doctor about all your medical conditions, including allergies.
The use of Ezetimibe and Atorvastatin Sandoz with fibrates (medicines used to lower cholesterol) should be avoided, as the combination has not been studied.

Children
The use of Ezetimibe and Atorvastatin Sandoz is not recommended in children and adolescents.

Other medicines and Ezetimibe and Atorvastatin Sandoz
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.
Some medicines may alter the effect of Ezetimibe and Atorvastatin Sandoz, or their effect may be altered by Ezetimibe and Atorvastatin Sandoz (see section 3). Such interactions could reduce the effectiveness of one or both medicines. Alternatively, they could increase the risk or severity of adverse effects, including the serious condition of muscle breakdown known as “rhabdomyolysis”, described in section 4:

• ciclosporin (a medicine often used in organ transplant patients)
• erythromycin, clarithromycin, telithromycin, fusidic acid**, rifampicin (medicines for bacterial infections)
• ketoconazole, itraconazole, voriconazole, fluconazole, posaconazole (medicines for fungal infections)
• gemfibrozil, other fibrates, nicotinic acid derivatives, colestipol, cholestyramine (other medicines used to regulate lipid levels)
• certain calcium channel blockers used for angina or hypertension, e.g., amlodipine and diltiazem
• digoxin, verapamil, amiodarone (medicines used to regulate heart rhythm)
• medicines used to treat HIV, e.g., ritonavir, lopinavir, atazanavir, indinavir, darunavir, the combination of tipranavir/ritonavir, etc. (medicines for AIDS)
• certain medicines used to treat hepatitis C, e.g., telaprevir, boceprevir, and the combination elbasvir/grazoprevir
• daptomycin (a medicine used to treat complicated skin infections, skin structure infections, and bacteremia)

** If you need to take oral fusidic acid to treat a bacterial infection, you must temporarily stop taking this medicine. Your doctor will advise you when it is safe to restart treatment with Ezetimibe and Atorvastatin Sandoz. Taking Ezetimibe and Atorvastatin Sandoz with fusidic acid may rarely cause muscle weakness, tenderness, or pain (rhabdomyolysis). See further information on rhabdomyolysis in section 4.
Other medicines known to interact with Ezetimibe and Atorvastatin Sandoz:

• oral contraceptives
• stiripentol (an anticonvulsant medicine used to treat epilepsy)
• cimetidine (a medicine used to treat heartburn and peptic ulcers)
• phenazone (a painkiller)
• antacids (medicines for digestive problems containing aluminium or magnesium)
• warfarin, phenprocoumon, acenocoumarol, or fluindione (medicines to prevent blood clots)
• colchicine (used to treat gout)
• St. John’s wort (a herbal medicine used to treat depression)

Ezetimibe and Atorvastatin Sandoz with food and alcohol
For instructions on how to take Ezetimibe and Atorvastatin Sandoz, see section 3. Pay attention to the following:
Grapefruit juice
Do not drink more than one or two small glasses of grapefruit juice per day, as large quantities of grapefruit juice may alter the effects of Ezetimibe and Atorvastatin Sandoz.
Alcohol
Avoid drinking excessive amounts of alcohol while being treated with this medicine. For further information, see section 2 “Warnings and precautions”.

Pregnancy and breastfeeding
Do not take Ezetimibe and Atorvastatin Sandoz if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. Do not take Ezetimibe and Atorvastatin Sandoz if you are a woman of childbearing age unless you are using an effective method of contraception. If you become pregnant while taking Ezetimibe and Atorvastatin Sandoz, stop treatment immediately and contact your doctor.
Do not take Ezetimibe and Atorvastatin Sandoz if you are breastfeeding.
The safety of Ezetimibe and Atorvastatin Sandoz during pregnancy and breastfeeding has not yet been established.
Ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines
Ezetimibe and Atorvastatin Sandoz is not expected to affect your ability to drive or operate machinery. However, bear in mind that some people may experience dizziness after taking Ezetimibe and Atorvastatin Sandoz.

Ezetimibe and Atorvastatin Sandoz contains lactose
Ezetimibe and Atorvastatin Sandoz tablets contain a sugar called lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

Ezetimibe and Atorvastatin Sandoz contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially “sodium-free”.

3. How to take Ezetimibe and Atorvastatina Sandoz

Take this medicine exactly as your doctor has told you. Your doctor will determine the appropriate dose for you based on your current treatment and individual risk factors.
If you have any doubts, consult your doctor or pharmacist.

• Before starting Ezetimibe and Atorvastatina Sandoz, you must follow a cholesterol-lowering diet.
• You must continue this cholesterol-lowering diet while being treated with Ezetimibe and Atorvastatina Sandoz.

How much to take
The recommended dose is one tablet of Ezetimibe and Atorvastatina Sandoz taken orally once daily. For adults, this is one capsule at the prescribed strength.

When to take it
Take Ezetimibe and Atorvastatina Sandoz at any time of day. You may take it with or without food.
If your doctor has prescribed Ezetimibe and Atorvastatina Sandoz together with colestyramine or another bile acid sequestrant, you must take Ezetimibe and Atorvastatina Sandoz at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more Ezetimibe and Atorvastatina Sandoz than you should
Contact your doctor or pharmacist.

If you forget to take Ezetimibe and Atorvastatina Sandoz
If you miss a dose, do not take a double dose. Take only the next dose at your usual time.

If you have any questions about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you notice any of the following serious side effects or symptoms, stop taking this medicine immediately and contact your doctor or go to the nearest hospital emergency department:

• Severe allergic reaction causing swelling of the face, tongue and throat, which may cause severe difficulty in breathing.
• Severe illness with extensive skin peeling and swelling, blistering of the skin, mouth, eyes, genitals, and fever. Skin rash with pink-red patches, particularly on the palms of the hands or soles of the feet, which may develop blisters.
• Muscle weakness, tenderness, pain or injury, or change in urine colour to red-brown, especially if you also feel unwell and have a high fever. This could be due to abnormal muscle breakdown, which can be life-threatening and lead to kidney problems.
• Lupus-like syndrome (including skin rash, joint disorders and effects on blood cells).

You should contact your doctor as soon as possible if you experience unexpected or unusual bleeding or bruising, as this may indicate a liver disorder.

The following common side effects have been reported (may affect up to 1 in 10 people):

• Diarrhoea
• Muscle pain

The following uncommon side effects have been reported (may affect up to 1 in 100 people):

• Influenza
• Depression, sleep problems, sleep disorders
• Dizziness, headache, tingling sensation
• Slow heart rate
• Hot flush
• Shortness of breath
• Abdominal pain, abdominal swelling, constipation, indigestion, frequent bowel movements, stomach inflammation, nausea, stomach discomfort, stomach disorder
• Acne, urticaria
• Joint pain, back pain, leg cramps, fatigue, muscle spasms or weakness; pain in arms and legs
• Unusual weakness, feeling tired or unwell, swelling especially in the ankles (oedema)
• Increases in certain blood test values indicating liver or muscle (CK) function
• Weight gain

In patients treated with Ezetimibe and Atorvastatin Sandoz or with ezetimibe or atorvastatin tablets, the following additional side effects have also been reported:

• Allergic reactions including swelling of the face, lips, tongue and/or throat, which may cause difficulty in breathing or swallowing (a condition requiring immediate intervention)
• Raised, red skin rash, sometimes accompanied by "target-like" lesions
• Liver problems
• Cough
• Heartburn
• Loss of appetite; decreased appetite
• High blood pressure
• Skin rash and itching; allergic reactions including skin rashes and urticaria
• Tendon injury
• Gallstones or inflammation of the gallbladder (which may cause abdominal pain, nausea and vomiting)
• Pancreatitis, often with severe abdominal pain
• Reduction in blood cell counts, which may lead to bruising/bleeding (thrombocytopenia)
• Nasal inflammation, nosebleeds
• Neck pain, pain, chest pain, throat pain
• Increased or decreased blood sugar levels (if you have diabetes, you should continue to monitor your blood sugar levels closely)
• Nightmares
• Numbness or tingling in fingers of hands and feet
• Reduced sensitivity to pain or touch
• Altered sense of taste, dry mouth
• Memory loss
• Ringing in the ears and/or head; hearing loss
• Vomiting
• Belching
• Hair loss
• Increased body temperature
• Urine tests positive for white blood cells
• Blurred vision; visual disturbances
• Gynaecomastia (enlargement of breast tissue in men)

Possible side effects reported with some statins:

• Sexual difficulties
• Depression
• Breathing problems including persistent cough and/or shortness of breath or fever
• Diabetes. More likely if you have high levels of sugar and fats in the blood, are overweight, or have high blood pressure. Your doctor will monitor you during treatment with this medicine.
• Persistent muscle pain, tenderness or weakness, particularly if you also feel unwell or have a high fever that does not resolve after stopping Ezetimibe and Atorvastatin Sandoz (frequency not known)
• Severe myasthenia (a disease causing generalized muscle weakness, which in some cases includes muscles used for breathing)
• Ocular myasthenia (a disease causing weakness of the eye muscles)

Contact your doctor if you experience worsening weakness in the arms or legs after periods of activity, double vision or drooping eyelids, difficulty swallowing or shortness of breath.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ezetimibe and Atorvastatatin Sandoz

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Ezetimibe and Atorvastatin Sandoz contains
Ezetimibe and Atorvastatin Sandoz 10 mg/10 mg film-coated tablets
Each film-coated tablet contains 10 mg of ezetimibe and 10 mg of atorvastatin (as atorvastatin
calcium trihydrate).
Ezetimibe and Atorvastatin Sandoz 10 mg/20 mg film-coated tablets
Each film-coated tablet contains 10 mg of ezetimibe and 20 mg of atorvastatin (as atorvastatin
calcium trihydrate).
Ezetimibe and Atorvastatin Sandoz 10 mg/40 mg film-coated tablets
Each film-coated tablet contains 10 mg of ezetimibe and 40 mg of atorvastatin (as atorvastatin
calcium trihydrate).
Ezetimibe and Atorvastatin Sandoz 10 mg/80 mg film-coated tablets
Each film-coated tablet contains 10 mg of ezetimibe and 80 mg of atorvastatin (as atorvastatin
calcium trihydrate).

The other components are:
Tablet core
microcrystalline cellulose 101 (E460), mannitol (E421), calcium carbonate (E170), sodium croscarmellose
(E468), hypromellose (E464), polysorbate 80 (E433), yellow iron oxide (E172), magnesium stearate
(E470b), povidone K29/32 (E1201), sodium lauryl sulfate (E487)
Tablet coating
Ezetimibe and Atorvastatin Sandoz 10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg – Opadry White OY-L-28900 consisting of:
Lactose monohydrate
Hypromellose 2910 (E464)
Titanium dioxide (E171)
Macrogol 4000 (E1521)
Ezetimibe and Atorvastatin Sandoz 10 mg/80 mg DrCoat FCU consisting of:
Hypromellose 2910 (E464)
Titanium dioxide (E171)
Talc (E553b)
Macrogol 4000
Yellow iron oxide (E172)

Description of the appearance of Ezetimibe and Atorvastatin Sandoz and contents of the pack
Ezetimibe and Atorvastatin Sandoz 10 mg/10 mg film-coated tablets: white, round, biconvex film-coated tablets with a diameter of approximately 8.1 mm.
Ezetimibe and Atorvastatin Sandoz 10 mg/20 mg film-coated tablets: white, oval-shaped, biconvex film-coated tablets with dimensions of approximately 11.6 x 7.1 mm.
Ezetimibe and Atorvastatin Sandoz 10 mg/40 mg film-coated tablets: white, capsule-shaped, biconvex film-coated tablets with dimensions of approximately 16.1 x 6.1 mm.
Ezetimibe and Atorvastatin Sandoz 10 mg/80 mg film-coated tablets: yellow, oblong, biconvex film-coated tablets with dimensions of approximately 19.1 x 7.6 mm.

Ezetimibe and Atorvastatin Sandoz 10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg film-coated tablets
OPA/Al/PVC//Al blister packs containing 30, 60, 100 or 120 film-coated tablets.
OPA/Al/PVC//Al blister packs divisible into single doses containing 30 x 1, 90 x 1 and 100 x 1 film-coated tablets.

Ezetimibe and Atorvastatin Sandoz 10 mg/80 mg film-coated tablets
OPA/Al/PVC//Al blister packs containing 30 tablets, multipacks containing 90 (2 packs of 45) and multipacks containing 100 (2 packs of 50) and multipacks containing 100 x 1 (2 packs of 50 x 1) film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder
Sandoz S.p.A.
Viale Luigi Sturzo 43
20154 Milan
Italy

Manufacturers
Elpen Pharmaceuticals Co. Inc.
Marathonos Avenue 95
19009, Pikermi, Greece
ELPEN Pharmaceutical Co. Inc.
Zapani, Block 1048
190 01, Keratea, Greece
Lek Pharmaceuticals d.d.
Verovskova Ulica 57
1526, Ljubljana, Slovenia

This medicinal product has been authorised in the Member States of the European Economic Area under the following names:

Netherlands
Ezetimibe/Atorvastatine Sandoz 10 mg/10 mg, filmomhulde tabletten
Ezetimibe/Atorvastatine Sandoz 10 mg/20 mg, filmomhulde tabletten
Ezetimibe/Atorvastatine Sandoz 10 mg/40 mg, filmomhulde tabletten
Ezetimibe/Atorvastatine Sandoz 10 mg/80 mg, filmomhulde tabletten

Belgium
Tymyzato 10 mg/10 mg filmomhulde tabletten
Tymyzato 10 mg/20 mg filmomhulde tabletten
Tymyzato 10 mg/40 mg filmomhulde tabletten
Tymyzato 10 mg/80 mg filmomhulde tabletten

Spain
Ezetimiba/Atorvastatina Sandoz Farmacéutica 10 mg/10 mg comprimidos recubiertos con película EFG
Ezetimiba/Atorvastatina Sandoz Farmacéutica 10 mg/20 mg comprimidos recubiertos con película EFG
Ezetimiba/Atorvastatina Sandoz Farmacéutica 10 mg/40 mg comprimidos recubiertos con película EFG
Ezetimiba/Atorvastatina Sandoz Farmacéutica 10 mg/80 mg comprimidos recubiertos con película EFG

France
EZETIMIBE/ATORVASTATINE SANDOZ 10 mg/10 mg, comprimé pelliculé
EZETIMIBE/ATORVASTATINE SANDOZ 10 mg/20 mg, comprimé pelliculé
EZETIMIBE/ATORVASTATINE SANDOZ 10 mg/40 mg, comprimé pelliculé
EZETIMIBE/ATORVASTATINE SANDOZ 10 mg/80 mg, comprimé pelliculé

Italy
Ezetimibe e Atorvastatina Sandoz

Portugal
Atorvastatina + Ezetimiba Sandoz Farmacêutica

Germany
Ezetimib/Atorvastatin - 1 A Pharma 10 mg/10 mg Filmtabletten
Ezetimib/Atorvastatin - 1 A Pharma 10 mg/20 mg Filmtabletten
Ezetimib/Atorvastatin - 1 A Pharma 10 mg/40 mg Filmtabletten
Ezetimib/Atorvastatin - 1 A Pharma 10 mg/80 mg Filmtabletten

Greece
Ancilleg

Lithuania
Ezetimibe/Atorvastatin Sandoz 10 mg/10 mg plevele dengtos tabletes
Ezetimibe/Atorvastatin Sandoz 10 mg/20 mg plevele dengtos tabletes
Ezetimibe/Atorvastatin Sandoz 10 mg/40 mg plevele dengtos tabletes

Poland
Ezetimibe + Atorvastatin Sandoz

Hungary
Ezetimibe/Atorvastatin 1 A Pharma 10 mg/10 mg filmtabletta
Ezetimibe/Atorvastatin 1 A Pharma 10 mg/20 mg filmtabletta
Ezetimibe/Atorvastatin 1 A Pharma 10 mg/40 mg filmtabletta
Ezetimibe/Atorvastatin 1 A Pharma 10 mg/80 mg filmtabletta

Romania
Ezetimib/Atorvastatina Sandoz 10 mg/10 mg comprimate filmate
Ezetimib/Atorvastatina Sandoz 10 mg/20 mg comprimate filmate
Ezetimib/Atorvastatina Sandoz 10 mg/40 mg comprimate filmate
Ezetimib/Atorvastatina Sandoz 10 mg/80 mg comprimate filmate

Slovakia
Ezetimib/Atorvastatín Sandoz 10 mg/10 mg
Ezetimib/Atorvastatín Sandoz 10 mg/20 mg
Ezetimib/Atorvastatín Sandoz 10 mg/40 mg
Ezetimib/Atorvastatín Sandoz 10 mg/80 mg